Dr Jonathan Peter

South Africa

EDCTP portfolio: Senior Fellowships

Professor Jonathan (Jonny) Peter is developing the capacity to identify – and ultimately prevent – rare immune-mediated adverse reactions to drugs.

A clearer picture of adverse drug reactions

Drugs shown to be safe and effective in clinical trials may nevertheless cause rare adverse reactions of varying degrees of severity. Adverse drug reactions may mean drug treatment has to be halted, and in the most severe cases can be life-threatening.

As genetic factors influence the risk of adverse drug reactions, their prevalence varies globally, emphasising the importance of regional studies. In addition, relatively little is known about their underlying mechanisms.

The challenge

Professor Jonny Peter is the first registered adult allergist in South Africa. He has been focusing on severe cutaneous adverse reactions (SCAR) – potentially deadly drug reactions affecting the skin. These are known to be mediated by the immune system and are relatively common in sub-Saharan Africa, in part because of the nature of the drugs used in the region and the impact of regionally prevalent infectious diseases – adverse reactions are 100-fold more common in people with HIV infections.

In his EDCTP Senior Fellowship, Professor Peter is building on an existing study monitoring for SCAR in South Africa, which is beginning to provide important data on reactions to antiretroviral and anti-TB drugs. He is now extending this work by developing a network, AfriSCAR, across five sub-Saharan African countries. This will enable data on the epidemiology of SCAR to be captured from four additional countries, as well as samples for laboratory analysis.

The fellowship will also enable Professor Peter to develop both his technical skills, particular in advanced immunology and ‘omics’ technologies, and his project management and leadership abilities. These skills will be passed on to a PhD and two master’s students involved in the project.

The project

Dr Peter’s Senior Fellowship project will reveal more about the prevalence of severe drug reactions in sub-Saharan Africa, and which drugs are most likely to trigger them – not straightforward when many patients are taking multiple medications. It will also shed light on possible genetic and immunological risk factors, which will improve understanding of underlying mechanisms and suggest new approaches to prevent or treat severe adverse reactions. In addition, it will create a regional network able to carry out clinical trials of new treatments or prevention of these devastating conditions.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Drugs shown to be safe and effective in clinical trials may nevertheless cause rare adverse reactions of varying degrees of severity. Adverse drug reactions may mean drug treatment has to be halted, and in the most severe cases can be life-threatening.

As genetic factors influence the risk of adverse drug reactions, their prevalence varies globally, emphasising the importance of regional studies. In addition, relatively little is known about their underlying mechanisms.

Professor Jonny Peter is the first registered adult allergist in South Africa. He has been focusing on severe cutaneous adverse reactions (SCAR) – potentially deadly drug reactions affecting the skin. These are known to be mediated by the immune system and are relatively common in sub-Saharan Africa, in part because of the nature of the drugs used in the region and the impact of regionally prevalent infectious diseases – adverse reactions are 100-fold more common in people with HIV infections.

In his EDCTP Senior Fellowship, Professor Peter is building on an existing study monitoring for SCAR in South Africa, which is beginning to provide important data on reactions to antiretroviral and anti-TB drugs. He is now extending this work by developing a network, AfriSCAR, across five sub-Saharan African countries. This will enable data on the epidemiology of SCAR to be captured from four additional countries, as well as samples for laboratory analysis.

The fellowship will also enable Professor Peter to develop both his technical skills, particular in advanced immunology and ‘omics’ technologies, and his project management and leadership abilities. These skills will be passed on to a PhD and two master’s students involved in the project.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

Dr Peter’s Senior Fellowship project will reveal more about the prevalence of severe drug reactions in sub-Saharan Africa, and which drugs are most likely to trigger them – not straightforward when many patients are taking multiple medications. It will also shed light on possible genetic and immunological risk factors, which will improve understanding of underlying mechanisms and suggest new approaches to prevent or treat severe adverse reactions. In addition, it will create a regional network able to carry out clinical trials of new treatments or prevention of these devastating conditions.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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